For this reason NIDA has developed a CREST (Clinical Rapid Evaluation Screening Trial) protocol to provide a needed incremental medication screening step between preclinical research and full blown expensive Phase III pivotal trials. While patients receive manual based psychotherapy, three medications are screened compared to unmatched placebo in an eight-week, 80-subject, four cell design trial. Other important features of the CREST protocol include collecting baseline measurements over a two week period and analyzing primary outcome measures (quantitative urine toxicology and clinical global improvement scales) in terms of a composite score of overall individual patient improvement.